Surviving slices of cerebral tissue will be maintained in vitro and exposed to hypoxia of varying degree and duration. The conditions will be defined in which reversible and irreversible alterations of excitatory and inhibitory synaptic transmission occur. Changes of extracellular ion activity induced by hypoxia will be recorded. The composition of the bathing medium will be systematically varied, and drugs will be administered in order to detect possible protection against hypoxia or aggravation of the hypoxic insult by these manipulations. The passive and active membrane properties of neurons will be tested for alterations during hypoxia. The capacity of presynaptic terminals to release transmitter substance during hypoxia will also be determined. These experiments were designed to define the relationship between oxygen deprivation and the deterioration of the function of mammalian central nervous tissue; and to determine the mechanism of such deterioration. Certain specific hypotheses concerning the mechanism of hypoxic insult will be tested.